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Archive for the ‘Immuno-Oncology & Genomics’ Category


Lectures by The 2017 Award Recipients of Warren Alpert Foundation Prize in Cancer Immunology, October 5, 2017, HMS, 77 Louis Paster, Boston

Top, from left: James Allison and Lieping Chen. Bottom, from left: Gordon Freeman, Tasuku Honjo, Arlene Sharpe.

The 2017 Warren Alpert Foundation Prize has been awarded to five scientists for transformative discoveries in the field of cancer immunology.

Collectively, their work has elucidated foundational mechanisms in cancer’s ability to evade immune recognition and, in doing so, has profoundly altered the understanding of disease development and treatment. Their discoveries have led to the development of effective immune therapies for several types of cancer.

The 2017 award recipients are:

  • James Allison, professor of immunology and chair of the Department of Immunology, The University of Texas MD Anderson Cancer Center
  • Lieping Chen, United Technologies Corporation Professor in Cancer Research and professor of immunobiology, of dermatology and of medicine, Yale University
  • Gordon Freeman, professor of medicine, Dana-Farber Cancer Institute, Harvard Medical School
  • Tasuku Honjo, professor of immunology and genomic medicine, Kyoto University
  • Arlene Sharpe, the George Fabyan Professor of Comparative Pathology, Harvard Medical School; senior scientist, department of pathology, Brigham and Women’s Hospital

The honorees will share a $500,000 prize and will be recognized at a day-long symposium on Oct. 5 at Harvard Medical School.

The Warren Alpert Foundation, in association with Harvard Medical School, honors trailblazing scientists whose work has led to the understanding, prevention, treatment or cure of human disease. The award recognizes seminal discoveries that hold the promise to change our understanding of disease or our ability to treat it.

“The discoveries honored by the Warren Alpert Foundation over the years are remarkable in their scope and potential,” said George Q. Daley, dean of Harvard Medical School. “The work of this year’s recipients is nothing short of breathtaking in its profound impact on medicine. These discoveries have reshaped our understanding of the body’s response to cancer and propelled our ability to treat several forms of this recalcitrant disease.”

The Warren Alpert Foundation Prize is given internationally. To date, the foundation has awarded nearly $4 million to 59 scientists. Since the award’s inception, eight honorees have also received a Nobel Prize.

“We commend these five scientists. Allison, Chen, Freeman, Honjoand Sharpe are indisputable standouts in the field of cancer immunology,” said Bevin Kaplan, director of the Warren Alpert Foundation. “Collectively, they are helping to turn the tide in the global fight against cancer. We couldn’t honor more worthy recipients for the Warren Alpert Foundation Prize.”

The 2017 award: Unraveling the mysterious interplay between cancer and immunity

Understanding how tumor cells sabotage the body’s immune defenses stems from the collective work of many scientists over many years and across multiple institutions.

Each of the five honorees identified key pieces of the puzzle.

The notion that cancer and immunity are closely connected and that a person’s immune defenses can be turned against cancer is at least a century old. However, the definitive proof and demonstration of the steps in this process were outlined through findings made by the five 2017 Warren Alpert prize recipients.

Under normal conditions, so-called checkpoint inhibitor molecules rein in the immune system to ensure that it does not attack the body’s own cells, tissues and organs. Building on each other’s work, the five award recipients demonstrated how this normal self-defense mechanism can be hijacked by tumors as a way to evade immune surveillance and dodge an attack. Subverting this mechanism allows cancer cells to survive and thrive.

A foundational discovery made in the 1980s elucidated the role of a molecule on the surface of T cells, the body’s elite assassins trained to seek, spot and destroy invaders.

A protein called CTLA-4 emerged as a key regulator of T cell behavior—one that signals to T cells the need to retreat from an attack. Experiments in mice lacking CTLA-4 and use of CTLA-4 antibodies demonstrated that absence of CTLA-4 or blocking its activity could lead to T cell activation and tumor destruction.

Subsequent work identified a different protein on the surface of T cells—PD-1—as another key regulator of T cell response. Mice lacking this protein developed an autoimmune disease as a result of aberrant T cell activity and over-inflammation.

Later on, scientists identified a molecule, B7-H1, subsequently renamed PD-L1, which binds to PD-1, clicking like a key in a lock. This was followed by the discovery of a second partner for PD-1—the molecule PD-L2—which also appeared to tame T-cell activity by binding to PD-1.

The identification of these molecules led to a set of studies showing that their presence on human and mouse tumors rendered the tumors resistant to immune eradication.

A series of experiments further elucidated just how tumors exploit the interaction between PD-1 and PD-L1 to survive. Specifically, some tumor cells appeared to express PD-L1, essentially “wrapping” themselves in it to avoid immune recognition and destruction.

Additional work demonstrated that using antibodies to block this interaction disarmed the tumors, rendering them vulnerable to immune destruction.

Collectively, the five scientists’ findings laid the foundation for antibody-based therapies that modulate the function of these molecules as a way to unleash the immune system against cancer cells.

Antibody therapy that targets CTLA-4 is currently approved by the FDA for the treatment of melanoma. PD-1/PD-L1 inhibitors have already shown efficacy in a broad range of cancers and have been approved by the FDA for the treatment of melanoma; kidney; lung; head and neck cancer; bladder cancer; some forms of colorectal cancer; Hodgkin lymphoma and Merkel cell carcinoma.

In their own words

“I am humbled to be included among the illustrious scientists who have been honored by the Warren Alpert Foundation for their contributions to the treatment and cure of human disease in its 30+ year history.  It is also recognition of the many investigators who have labored for decades to realize the promise of the immune system in treating cancer.”
        -James Allison


“The award is a great honor and a wonderful recognition of our work.”
         Lieping Chen



I am thrilled to have made a difference in the lives of cancer patients and to be recognized by fellow scientists for my part in the discovery of the PD-1/PD-L1 and PD-L2 pathway and its role in tumor immune evasion.  I am deeply honored to be a recipient of the Alpert Award and to be recognized for my part in the work that has led to effective cancer immunotherapy. The success of immunotherapy has unleashed the energies of a multitude of scientists to further advance this novel strategy.”
                                        -Gordon Freeman


I am extremely honored to receive the Warren Alpert Foundation Prize. I am very happy that our discovery of PD-1 in 1992 and subsequent 10-year basic research on PD-1 led to its clinical application as a novel cancer immunotherapy. I hope this development will encourage many scientists working in the basic biomedical field.”
-Tasuku Honjo


“I am truly honored to be a recipient of the Alpert Award. It is especially meaningful to be recognized by my colleagues for discoveries that helped define the biology of the CTLA-4 and PD-1 pathways. The clinical translation of our fundamental understanding of these pathways illustrates the value of basic science research, and I hope this inspires other scientists.”
-Arlene Sharpe

Previous winners

Last year’s award went to five scientists who were instrumental in the discovery and development of the CRISPR bacterial defense mechanism as a tool for gene editing. They were RodolpheBarrangou of North Carolina State University, Philippe Horvath of DuPont in Dangé-Saint-Romain, France, Jennifer Doudna of the University of California, Berkeley, Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Berlin and Umeå University in Sweden, and Virginijus Siksnys of the Institute of Biotechnology at Vilnius University in Lithuania.

Other past recipients include:

  • Tu Youyou of the China Academy of Chinese Medical Science, who went on to receive the 2015 Nobel Prize in Physiology or Medicine with two others, and Ruth and Victor Nussenzweig, of NYU Langone Medical Center, for their pioneering discoveries in chemistry and parasitology of malaria and the translation of their work into the development of drug therapies and an anti-malarial vaccine.
  • Oleh Hornykiewicz of the Medical University of Vienna and the University of Toronto; Roger Nicoll of the University of California, San Francisco; and Solomon Snyder of the Johns Hopkins University School of Medicine for research into neurotransmission and neurodegeneration.
  • David Botstein of Princeton University and Ronald Davis and David Hogness of Stanford University School of Medicine for contributions to the concepts and methods of creating a human genetic map.
  • Alain Carpentier of Hôpital Européen Georges-Pompidou in Paris and Robert Langer of MIT for innovations in bioengineering.
  • Harald zur Hausen and Lutz Gissmann of the German Cancer Research Center in Heidelberg for work on the human papillomavirus (HPV) and cancer of the cervix. Zur Hausenand others were honored with the Nobel Prize in Physiology or Medicine in 2008.

The Warren Alpert Foundation

Each year the Warren Alpert Foundation receives between 30 and 50 nominations from scientific leaders worldwide. Prize recipients are selected by the foundation’s scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School.

Warren Alpert (1920-2007), a native of Chelsea, Mass., established the prize in 1987 after reading about the development of a vaccine for hepatitis B. Alpert decided on the spot that he would like to reward such breakthroughs, so he picked up the phone and told the vaccine’s creator, Kenneth Murray of the University of Edinburgh, that he had won a prize. Alpert then set about creating the foundation.

To award subsequent prizes, Alpert asked Daniel Tosteson (1925-2009), then dean of Harvard Medical School, to convene a panel of experts to identify scientists from around the world whose research has had a direct impact on the treatment of disease.

SOURCE

https://hms.harvard.edu/news/warren-alpert-foundation-honors-pioneers-cancer-immunology

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Koch Institute Immune Engineering Symposium on October 16 & 17, 2017, Kresge, MIT

Reporter: Aviva Lev-Ari, PhD, RN

 

Koch Institute Immune Engineering Symposium on October 16 & 17, 2017.

 

Summary: Biological, chemical, and materials engineers are engaged at the forefront of immunology research. At their disposal is an analytical toolkit honed to solve problems in the petrochemical and materials industries, which share the presence of complex reaction networks, and convective and diffusive molecular transport. Powerful synthetic capabilities have also been crafted: binding proteins can be engineered with effectively arbitrary specificity and affinity, and multifunctional nanoparticles and gels have been designed to interact in highly specific fashions with cells and tissues. Fearless pursuit of knowledge and solutions across disciplinary boundaries characterizes this nascent discipline of immune engineering, synergizing with immunologists and clinicians to put immunotherapy into practice.

SPEAKERS:

Michael Birnbaum – MIT, Koch Institute

Arup Chakraborty – MIT, Insititute for Medical Engineering & Sciences

Jianzhu Chen – MIT, Koch Institute

Jennifer R. Cochran – Stanford University

Jennifer Elisseeff – Johns Hopkins University

K. Christopher Garcia – Stanford University

George Georgiou – University of Texas at Austin

Darrell Irvine – MIT, Koch Institute

Tyler Jacks – MIT, Koch Institute

Doug Lauffenburger – MIT, Biological Engineering and Koch Institute

Wendell Lim – University of California, San Francisco

Harvey Lodish – Whitehead Institute and Koch Institute

Marcela Maus – Massachusetts General Hospital

Garry P. Nolan – Stanford University

Sai Reddy – ETH Zurich

Nicholas Restifo – National Cancer Institute

William Schief – The Scripps Research Institute

Stefani Spranger – MIT, Koch Institute

Susan Napier Thomas – Georgia Institute of Technology

Laura Walker – Adimab, LLC

Jennifer Wargo – MD Anderson Cancer Center

Dane Wittrup – MIT, Koch Institute

Kai Wucherpfennig – Dana-Farber Cancer Institute

Please contact ki-events@mit.edu with any questions.

SOURCE

From: Koch Institute Immune Engineering Symposium <ki-events@mit.edu>

Reply-To: <ki-events@mit.edu>

Date: Friday, September 8, 2017 at 9:06 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Reminder – Register Today

 

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Announcing our 10th e-Book on Amazon.com – 1st day, 9/4/2017

Editor-in-Chief: Aviva Lev-Ari, PhD, RN

 

On our Book Shelf on Amazon.com

WE ARE ON AMAZON.COM

https://www.amazon.com/s/ref=dp_byline_sr_ebooks_9?ie=UTF8&text=Aviva+Lev-Ari&search-alias=digital-text&field-author=Aviva+Lev-Ari&sort=relevancerank

http://www.amazon.com/dp/B00DINFFYC

http://www.amazon.com/dp/B018Q5MCN8

http://www.amazon.com/dp/B018PNHJ84

http://www.amazon.com/dp/B018DHBUO6

http://www.amazon.com/dp/B013RVYR2K

http://www.amazon.com/dp/B012BB0ZF0

http://www.amazon.com/dp/B019UM909A

http://www.amazon.com/dp/B019VH97LU

http://www.amazon.com/dp/B071VQ6YYK

https://www.amazon.com/dp/B075CXHY1B

 

The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: VOLUME 2: Infectious Diseases and Therapeutics and VOLUME 3: The Immune System and Therapeutics (Series D: BioMedicine & Immunology) Kindle Edition – on Amazon.com since 9/4/2017

by Larry H. Bernstein (Author), Aviva Lev-Ari (Author), Stephen J. Williams (Author), Demet Sag (Author), Irina Robu (Author), Tilda Barliya (Author), David Orchard-Webb (Author), Alan F. Kaul (Author), Danut Dragoi (Author), Sudipta Saha (Editor)

https://www.amazon.com/dp/B075CXHY1B

 

Product details

  • File Size:21832 KB
  • Print Length:3747 pages
  • Publisher:Leaders in Pharmaceutical Business Intelligence (LPBI) Group; 1 edition (September 4, 2017)
  • Publication Date:September 4, 2017
  • Sold by:Amazon Digital Services LLC
  • Language:English
  • ASIN:B075CXHY1B
  • Text-to-Speech: Enabled 
  • X-Ray: Not Enabled 
  • Word Wise:Not Enabled
  • Lending:Enabled
  • Enhanced Typesetting:Not Enabled 

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FDA has approved the world’s first CAR-T therapy, Novartis for Kymriah (tisagenlecleucel) and Gilead’s $12 billion buy of Kite Pharma, no approved drug and Canakinumab for Lung Cancer (may be?)

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 9/7/2017

Here’s the inside account of Gilead’s 11-week sprint to its $12B Kite buyout – ENDPOINTS NEWS

UPDATED on 8/31/2017

Gilead-Kite: A New Transformative Deal For Biotech, AUG 30, 2017

Gilead has made a big bet on new technology in Kite’s immunotherapy platforms and has reduced the number of credible large players in the space.

With a reputation for intense diligence and dynamism in its business development efforts, Gilead’s management team will only bolster the immunotherapy field as it prepares to face off with Novartis, its immediate competitor, and enters squarely in the province of Merck and Bristol Myers Squibb, two of the leaders in immuno-oncology.

Gilead has reinvented the transformative transaction for the sector.

https://www.forbes.com/sites/stephenbrozak/2017/08/30/gilead-kite-a-new-transformative-deal-and-maybe-the-new-future-of-healthcare-deals/#fc64fca65d49

 

I attended this week the Cambridge Healthtech Institute’s 4th Annual

Adoptive T Cell Therapy

Delivering CAR, TCR, and TIL from Research to Reality
August 29 – 30, 2017 | Sheraton Boston | Boston, MA

 

The following talks on 8/29/2017 presented the frontier of CAR-T Therapies and Technologies from lab to bed side:

  • Building Better T Cell Therapies: The Power of Molecular Profiling

Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics

  • Tricked-Out Cars, the Next Generation of CAR T Cells

Richard Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio

  • The Generation of Lentiviral Vector-Modified CAR-T Cells Using an Automated Process

Boro Dropulic, Ph.D., General Manager and CSO, Lentigen Technology, Inc.

I covered this event in Real Time for the Press

LIVE – 8/29 – CHI’s Oncolytic Virus Immunotherapy and ADOPTIVE CELL THERAPY, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA

https://pharmaceuticalintelligence.com/2017/08/29/live-829-chis-oncolytic-virus-immunotherapy-and-adoptive-cell-therapy-august-28-29-2017-sheraton-boston-hotel-boston-ma/

 

One year ago we published the following:

What does this mean for Immunotherapy? FDA put a temporary hold on Juno’s JCAR015, Three Death of Celebral Edema in CAR-T Clinical Trial and Kite Pharma announced Phase II portion of its CAR-T ZUMA-1 trial

https://pharmaceuticalintelligence.com/2016/07/09/what-does-this-mean-for-immunotherapy-fda-put-a-temporary-hold-on-jcar015-three-death-of-celebral-edema-in-car-t-clinical-trial-and-kite-pharma-announced-phase-ii-portion-of-its-car-t-zuma-1-trial/

 

SOURCE

Is Canakinumab the Next Viagra?

In this Revolution and Revelation, Milton Packer explains how safety data can sometimes trump a primary endpoint

by Milton PackerAugust 30, 2017

https://www.medpagetoday.com/Blogs/RevolutionandRevelation/67605

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CHI’s 5th ImmunoModulatory Therapeutic Antibodies for Cancer Conference, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA

Reporter: Aviva Lev-Ari, PhD, RN

ANNOUNCEMENT

Leaders in Pharmaceutical Business Intelligence (LPBI) Group will cover the event in

REAL TIME

Aviva Lev-Ari, PhD, RN will be streaming live from the floor of the Sheraton Hotel in Boston on August 28 and August 29, 2017

@pharma_BI

@AVIVA1950

 

Cambridge Healthtech Institute’s 5th Annual

Immunomodulatory Therapeutic Antibodies for Cancer

Scientific Strategies for Discovering and Developing Novel Immunotherapies and Agents to Improve the Efficacy and Toxicology Profiles of T Cell-Targeted Biotherapeutics
August 28-29, 2017 Sheraton Boston Hotel | Boston, MA

http://www.immuno-oncologysummit.com/Immunomodulatory-Antibodies-Cancer/

 

MONDAY, AUGUST 28

7:30 am Registration & Morning Coffee

8:25 Chairperson’s Opening Remarks

Yan Qu, Ph.D., Senior Principal Scientist, Pfizer

 

8:30 KEYNOTE PRESENTATION: Enabling Effective Immuno-Oncology

Greg_AdamsGregory Adams, Ph.D., CSO, Eleven Biotherapeutics

Checkpoint inhibitors and other immune-oncology agents have shown significant promise in the treatment of a variety of cancers. However, many of these agents are only effective when an existing host immune response has already been induced by other therapeutic approaches. I will discuss strategies that may be used to effectively set the stage for immune-oncology treatments including Eleven BioTherapeutics’ Targeted Protein Therapeutics.

9:00 Immunomodulatory Antibodies – Potentiation by Fc Receptor Engagement

Rony_DahanRony Dahan, Ph.D., Principal Investigator, Immunology, Weizmann Institute of Science, Israel

Immunomodulatory mAbs are revolutionizing cancer treatment due to their clinical effective stimulation of therapeutic anti-cancer immunity. Recent studies demonstrated the importance of the Fc domain of these types of mAbs. Their optimal activity can be critically depended on their ability to engage defined FcgR pathways. I will discuss our recent characterization of these FcgR-dependent mechanisms, and how they can be exploited for introducing second generation Fc-optimized immunomodulatory mAbs.

TD2 tagline9:30 Coffee Break

 

MECHANISMS OF ACTION

10:00 The Role of Metabolism in Immune Response in Tumors: Merging the Past and the Present of Tumor Microenvironment

Allison_BetofAllison S. Betof, M.D., Ph.D., Medical Oncology Fellow, Memorial Sloan Kettering Cancer Center

Tumors are not simply collections of cancer cells that arise in a vacuum; they are instead complex structures composed of blood vessels, immune cells, and other supporting structures that interact, consume oxygen and other nutrients, and produce waste. Tumor metabolism has long been viewed as a therapeutic target. I will discuss recent data on how metabolism influences immunobiology and our group’s approach to harness these interactions to improve therapeutic outcomes.

10:30 PI3Kgamma Is a Molecular Switch that Controls Immune Suppression

Megan_KanedaMegan M. Kaneda, Ph.D., Assistant Project Scientist, University of California, San Diego

Macrophages play critical but opposite roles in inflammation and cancer. We have found that the predominant isoform of PI3K in myeloid cells, PI3Kgamma, controls the switch between immune stimulation and immune suppression. Inhibition of macrophage PI3Kgamma activity promotes an immunostimulatory transcriptional program that restores CD8+ T cell activation and cytotoxicity and synergizes with checkpoint inhibitor therapy to promote tumor regression and extend survival in mouse models of cancer.

11:00 Avelumab (hIgG1 Anti-human PD-L1) Mediates the anti-Tumor Efficacy via Multiple Pathways in Preclinical Models

Yan_QuYan Qu, Ph.D., Senior Principal Scientist, Pfizer

Analysis of PD-L1 expression on various immune subpopulations in human patient samples showed that PD-L1 is enriched on non-T cells. In tumor-bearing mice, the percentage of splenic NK cells was increased with WT avelumab treatment but not with the Fc isotype variant. Avelumab-induced tumor shrinkage, tumor-infiltrating CD8+ T cell increase, and tumor PD-L1+ immature myeloid cell decrease appear to require NK cells, as such changes were abolished upon NK depletion.

ProImmune11:30 Epitope Identification and Clinical Immune Monitoring in Immune Oncology Programs

Emilee KnowltonEmilee Knowlton, Ph.D., Immunology Sales Specialist, ProImmune

 

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:30 Session Break

TARGET DISCOVERY FOR NEXT GENERATION IMMUNOTHERAPIES

1:25 Chairperson’s Remarks

Stephen Beers, Ph.D., Associate Professor, Cancer Immunology and Immunotherapy, University of Southampton, United Kingdom

1:30 Functional Characterization of Macaque Fcr and IgG Subtypes

Margie Ackerman, Ph.D., Assistant Professor, Engineering, Dartmouth College

A number of antibody therapies rely on Fc receptor (FcR)-mediated effector functions for optimal activity, prompting the need to understand how native and IgG domains engineered to differentially bind to the human receptors translate in non-human primate (NHP) models. We report characterization of the affinity between an IgG Fc variant panel (including subclass, Fc mutants and glycosylation) and major human and rhesus FcR allotypic variants.

2:00 Utilizing Patient-Derived Organoids and High-Content Imaging for Screening and Characterization of Bispecific Antibodies

Mark_ThrosbyMark Throsby, Ph.D., EVP & CSO, Merus N.V., The Netherlands

This presentation will provide a case study on how panels of patient-derived organoids grown ex-vivo in 3D culture combined with high-content imaging can be applied to bispecific antibody screening. Lead candidate bispecifics were selected targeting the wnt pathway with novel modes of action including immunomodulation.

 

2:30 Discovery and Development Strategies for New Small Molecule Immunotherapies

Nicola_WallisNicola Wallis, Ph.D., Senior Director, Biology, Astex Therapeutics, Ltd.

Small molecules are of interest as immunotherapies as both single agent and combinations, offering the possibility of modulating different aspects of the immune system to biologics. We are exploring targeting a number of different immunomodulatory mechanisms with small molecules derived using fragment-based drug design and will describe examples in this presentation.

TD2 tagline3:00 Refreshment Break

 

IMMUNE SYSTEM PRIMING AND ACTIVATION

3:30 STING Adjuvants for Immune System Priming for Antibody Therapy

Stephen_BeersStephen Beers, Ph.D., Associate Professor, Cancer Immunology and Immunotherapy, University of Southampton, United Kingdom

Successful tumor-targeting antibody approaches appear to rely predominantly on the effector function of Fcγ receptor (FcγR) expressing macrophages. Unfortunately, tumor-associated macrophages (TAM) are frequently poorly cytotoxic, contribute to immune suppression and have suboptimal FcγR expression making treatment less effective. Here we show that STING agonists are able to overcome immunosuppression in the tumour microenvironment effectively reversing the TAM inhibitory FcγR profile and provided strong adjuvant effects to antibody therapy.

4:00 Next-Generation Cancer Vaccines

Daniel_LeveyDaniel L. Levey, Ph.D., Senior Director, Vaccine Research, Agenus

Agenus is advancing two fully synthetic cancer vaccine platforms. The first is based on identification of mutations encoded in the tumor genome while the second relates to a novel class of tumor specific neo-epitopes arising from inappropriate phosphorylation of various proteins in malignant cells. The platforms support the manufacture of both individualized and off-the-shelf cancer vaccines against a range of tumor antigens, increasing the likelihood of immune recognition of tumors.

4:30 Oral T Cell Vaccines Targeting Immune Organs of the Gut for Generating Systemic Antigen Specific T Cells

Marc_MansourMarc Mansour, Ph.D., Chief Business Officer, Vaximm AG

We use attenuated Salmonella typhi Ty21 as a vector to deliver a plasmid encoding antigens of interest via the oral route to Peyer’s patches. The bacteria have built in adjuvant properties and induce cross presentation to produce a systemic T cell response. Monotherapy with a candidate targeting VEGFR2 produced clinical responses in GBM, highlighting the unique properties of this T cell vaccine approach.

5:00 End of Day

 

 

TUESDAY, AUGUST 29

7:25 am Breakout Discussion Groups with Continental Breakfast

Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are below.

New Understandings of the Mechanisms of Action for Immunomodulatory Antibodies

Moderator: Stephen Beers, Ph.D., Associate Professor, Cancer Immunology and Immunotherapy, University of Southampton, United Kingdom

  • What are we learning about MOA from clinical trial data?
  • Optimizing MOA in next generation immunomodulators
  • The role of effector and receptor engagement
  • MOA and bispecific antibody design
  • Overcoming resistance mechanisms

Target Discovery for Next Generation Immunotherapies

Marc Mansour, Ph.D., Chief Business Officer, Vaximm AG

  • Tumor antigen identification: strengths and weaknesses of different methodologies
  • Drugable IO targets- using macromolecules versus small molecule
  • Novel targets in the tumor microenvironment

NON-RESPONDERS, SIDE EFFECTS AND TOXICOLOGY

8:25 Chairperson’s Opening Remarks

Adam J. Adler, Ph.D., Professor, Immunology, University of Connecticut

8:30 Cancer Immunotherapy with Live-attenuated, Double Deleted Listeria Monocytogenes (LADD) Combination Strategies for the Treatment of Malignant Pleural Mesothelioma

Chan_WhitingChan C. Whiting, Ph.D., Director, Immune Monitoring and Biomarker Development, Aduro Biotech

We are advancing CRS-207, a clinical LADD strain engineered to express mesothelin, in combinations with various modalities for the treatment of malignant pleural mesothelioma.  Data from a Phase 1b study combining CRS-207 with standard chemotherapy demonstrating encouraging clinical and immune responses will be discussed.  An overview of the Phase 2 study design and progress of the CRS-207/Pembrolizumab combination study will also be highlighted.

9:00 Tumor and Class-Specific Patterns of Immune-Related Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review

Aaron_HansenAaron Hansen, M.D., Ph.D., Assistant Professor, Department of Medicine, University of Toronto; Medical Oncologist, Princess Margaret Cancer Center

Through a systematic review, we identified distinct immune related adverse event (irAE) profiles based on tumor type and immune checkpoint inhibitor class (CTLA-4 and PD-1). CTLA-4 inhibitors have a higher frequency of grade 3/4 irAEs. Furthermore, for patients treated with PD-1 inhibitors, those with melanoma had a higher frequency of gastrointestinal and skin irAEs, and lower rate of pneumonitis compared with patients with NSCLC and RCC. Different immune microenvironments may drive histology-specific irAE patterns.

PROTEIN ENGINEERING

9:30 Combination Therapy with PD-1 Blockade Enhances the Antitumor Potency of T Cells Redirected by Novel Bispecific Antibodies

Ken_ChangKen Chang, Ph.D., Vice President, Research and Development, Immunomedics

Novel bispecific antibodies that bind bivalently to tumor antigens and monovalently to CD3 can redirect T cells to kill Trop-2- or CEACAM5-expressing solid cancer cells grown in monolayer cultures at low picomolar concentrations. The antitumor efficacy was demonstrated also in a humanized mouse model and in 3D spheroids generated with cells from TNBC and colonic cancers. Combining anti-PD-1 increased cell death in 3D spheroids and prolonged survival of tumor-bearing animals.

MaxCyte no tagline10:00 Accelerated Production of Immunomodulatory Therapeutic Antibodies & Bispecific Molecules Using Scalable Cell Engineering

James_BradyJames Brady, Ph.D., Vice President, Technical Applications & Customer Support, MaxCyte

Antibodies and antibody-like molecules are a proven means of modulating effective anti-tumor immune responses. MaxCyte’s delivery platform facilitates rapid, fully scalable, high quality transient protein production in the cell line-of-choice, as well as streamlined stable pool and cell line generation enabling accelerated development of relevant immunomodulatory candidates. Case studies will illustrate the identification and development of antibodies, tribodies & bi-specific T cell engaging molecules (BiTEs) using the MaxCyte platform.

10:30 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

11:15 A Novel, Dual-Specific Antibody Conjugate Targeting CD134 and CD137 Costimulates T Cells and Elicits Antitumor Immunity

Adam_AdlerAdam J. Adler, Ph.D., Professor, Immunology, University of Connecticut

Combining agonists to different costimulatory receptors can be more effective in controlling tumors compared to individual agonists, but presents logistical challenges and increases the potential for adverse events. We developed a novel immunotherapeutic agent by fusing agonists to CD134 and CD137 into a single biologic, OrthomAb, that potentiates cytokine secretion from TCR-stimulated T cells more potently than non-conjugated CD134 + CD137 agonists in vitro, and reduces tumor growth in vivo.

11:45 Targeted Tissue Delivery Using Caveolae Technology Improves Drug Efficacy

Ruchi_GuptaRuchi Gupta, Ph.D., Team Lead Scientist, MedImmune

Current biotherapeutics focus on the molecular targets expressed on cells/tumors. However, less than 10% of the IV administrated biologics can reach the diseased tissues. Tissue targeting using caveolae proteins can allow for specific delivery to organs of interest. This talk will focus on caveolae technology that shows specific delivery to lungs and kidneys and improves drug efficacy. This targeting holds potential for several diseases including fibrosis, COPD, Infections as well as tumors.

12:15 pm Close of Immunomodulatory Therapeutic Antibodies for Cancer

 

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FDA: CAR-T therapy outweigh its risks tisagenlecleucel, manufactured by Novartis of Basel – 52 out of 63 participants — 82.5% — experienced overall remissions – young patients with Leukaemia [ALL]

 

Reporter: Aviva Lev-Ari, PhD, RN

 

Basel, July 12, 2017 – Novartis announced today that the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) unanimously (10-0) recommended approval of CTL019 (tisagenlecleucel), an investigational chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).

“The panel’s unanimous recommendation in favor of CTL019 moves us closer to potentially delivering the first-ever commercially approved CAR-T cell therapy to patients in need,” said Bruno Strigini, CEO, Novartis Oncology. “We’re very proud to be expanding new frontiers in cancer treatment by advancing immunocellular therapy for children and young adults with r/r B-cell ALL and other critically ill patients who have limited options. We look forward to working with the FDA as they complete their review.”

Acute lymphoblastic leukemia comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US[1]. Effective treatment options for patients with r/r ALL are limited. In pediatric and young adult patients with B-cell ALL that have relapsed multiple times or become refractory to treatment, the five-year disease-free survival is less than 10-30%[2],[3],[4].

CTL019 was first developed by the University of Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of CTL019 after it is infused into the patient, which may be associated with long-lasting remissions in patients. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including CTL019, for the investigational treatment of cancers. Children’s Hospital of Philadelphia (CHOP) was the first institution to investigate CTL019 in the treatment of pediatric patients and led the single site trial.

SOURCE

https://www.novartis.com/news/media-releases/novartis-car-t-cell-therapy-ctl019-unanimously-10-0-recommended-approval-fda

RISKS:

During the 2015 tisagenlecleucel trial, 47% of participants experienced an

  • extreme inflammatory reaction known as cytokine release syndrome, severe cases of which are called cytokine storms. The syndrome — characterized by symptoms such as high fevers and organ failure — can be life-threatening. But
  • Novartis says trial clinicians were able to manage the reaction successfully in all cases.
  • Neurological problems such as seizures and hallucinations were also relatively common but temporary,
  • the Novartis team reported. This is in stark contrast to some other CAR-T trials that have,
  • over the past year, reported the deaths of several participants from severe brain swelling.
  • Novartis’s therapy is not identical to the CAR-T cells used in those trials, which were administered in adults, but the deaths cast a pall over the entire field.

To generate a batch of tisagenlecleucel, white blood cells are purified from a sample of a patient’s blood and shipped to a central processing centre. There, staff use a virus to insert into the T cells genes that encode a cellular receptor — called a chimaeric antigen receptor — that will recognize leukaemia cells.

SOURCE

Engineered cell therapy for cancer gets thumbs up from FDA advisers

Treatment shows promise in young people with leukaemia, but safety risks abound.

Heidi Ledford, 12 July 2017

http://www.nature.com/news/engineered-cell-therapy-for-cancer-gets-thumbs-up-from-fda-advisers-1.22304?WT.ec_id=NEWSDAILY-20170713

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